Shen Zhuojian, Chen Baishen, Gan Xiangfeng, Hu Weicheng, Zhong Guangzheng, Li Haifeng, Xie Xuan, Liu Yeqing, Li Haigang, Xu Xia, Huang Zhiquan, Chen Ju
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, PR China; Lung Cancer Research Center of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou 510275, PR China.
Department of Thoracic Surgery, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 750004, PR China.
Biochem Biophys Res Commun. 2016 Feb 12;470(3):627-634. doi: 10.1016/j.bbrc.2016.01.094. Epub 2016 Jan 20.
The role of NEFL in NSCLC remains largely unknown. Immunohistochemistry was performed to investigate the expression of NEFL in 108 lung cancer specimens. NEFL expression was associated with decreased lymph node metastases and favorable prognosis. Furthermore, real-time PCR and Western blot were used to investigate the expression of the NEFL gene in NSCLC cell lines. Subsequently, lentivirus-mediated RNA interference and overexpression were used to demonstrate that knocked-down of NEFL enhanced the invasion and migration of A549 and H460 NSCLC cells, whereas NEFL overexpression resulted in a suppression of the invasion and migration of GLC-82 and L78 cells in vitro. In addition, bisulfite sequence PCR assay demonstrated that NEFL downregulation was associated with promoter methylation, and NEFL expression was restored after treatment with 5-Aza-dC. Finally, we demonstrated that NEFL inhibited the NF-κB pathway, thereby suppressing the expression of uPA and decreasing NSCLC invasiveness and migration. Our studies suggest that NEFL methylation is a novel mechanism for NSCLC invasion and metastasis and that NEFL may represent a candidate biomarker for recurrence and survival in patients with NSCLC.
